Invertible enantioselectivity in 6′-deoxy-6′-acylamino-β- isocupreidine-catalyzed asymmetric aza-Morita-Baylis-Hillman reaction: Key role of achiral additive

Article abstract of DOI:10.1021/ol901920s

The β-ICD (1a) or β-ICD-amide (1e)-catalyzed aza-Morlta-Baylls- Hlllman reaction between N-sulfonylimines 3 and alkyl vinyl ketones 4 produced the (R)-enriched adducts 5. By adding a catalytic amount of β-naphthol (2a), the enantloselectivity of the same

Full text of DOI:10.1021/ol901920s

ORGANIC
LETTERS
2009
Vol. 11, No. 20
4648-4651
Invertible Enantioselectivity in 6′-Deoxy-
6′-acylamino-ꢀ-isocupreidine-Catalyzed
Asymmetric Aza-Morita-Baylis-Hillman
Reaction: Key Role of Achiral Additive
Nacim Abermil, Ge´raldine Masson,* and Jieping Zhu*
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-YVette Cedex, France
zhu@icsn.cnrs-gif.fr; masson@icsn.cnrs-gif.fr
Received August 18, 2009
ABSTRACT
The ꢀ-ICD (1a) or ꢀ-ICD-amide (1e)-catalyzed aza-Morita-Baylis-Hillman reaction between N-sulfonylimines 3 and alkyl vinyl ketones 4 produced
the (R)-enriched adducts 5. By adding a catalytic amount of ꢀ-naphthol (2a), the enantioselectivity of the same reaction was inversed leading
to (S)-5 in excellent yields and enantioselectivities. Both aromatic and aliphatic imines are accepted as substrates for this reaction.
The aza-Morita-Baylis-Hillman reaction (aza-MBH) pro-
duces R-methylene-ꢀ-aminocarbonyl derivatives from simple
imines and electron-deficient alkenes in an atom-economic
fashion.1 During the past decade, this reaction has been
extensively investigated especially in its catalytic asymmetric
version2 due to the high synthetic value of its adduct. The
ꢀ-isocupreidine (ꢀ-ICD 1a), originally synthesized by Hoff-
mann3 and developed by Hatakeyama for enantioselective
MBH reaction,4 has later been demonstrated to be one of
the most efficient catalysts for the aza-MBH reaction thanks
to the work of Shi,5 Hatakeyama,6 and Adolfsson.7 Not-
withstanding the catalytic efficiency and the broad ap-
plicability of ꢀ-ICD, one serious drawback is that the
enantiomer or pseudoenantiomer of 1a is not easily avail-
(3) (a) Braje, W.; Frakenpohl, J.; Langer, P.; Hoffmann, H. M. R.
Tetrahedron 1998, 54, 3495. (b) Hoffmann, H. M. R.; Frackenpohl, J. Eur.
J. Org. Chem. 2004, 4293. (c) Marcelli, T.; van Maarseveen, J. H.; Hiemstra,
H. Angew. Chem., Int. Ed. 2006, 45, 7496. (d) Doyle, A. G.; Jacobsen,
E. N. Chem. ReV. 2007, 107, 5713. (e) Gaunt, M. J.; Johansson, C. C. C.
Chem. ReV. 2007, 107, 5596. (f) France, S.; Guerin, D. J.; Miller, S. J.;
Lectka, T. Chem. ReV. 2003, 103, 2985ꢀ-ICD was used as an efficient
catalyst in other reactions. See, for example: (g) Saaby, S.; Bella, M.;
Jørgensen, K. A. J. Am. Chem. Soc. 2004, 126, 8120. (h) Van stennis,
D. J. V. C.; Marcelli, T.; Lutz, M.; Speck, A. J.; van Maarseveen, J. H.;
Hiemstra, H. AdV. Synth. Catal. 2007, 349, 281.
(4) (a) Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.; Hatakeyama, S.
J. Am. Chem. Soc. 1999, 121, 10219. (b) Iwabuchi, Y.; Hatakeyama, S. J.
Synth. Org. Chem. Jpn. 2002, 60, 2. (c) Nakano, A.; Kawahara, S.;
Akamatsu, S.; Morokuma, K.; Nakatani, M.; Iwabuchi, Y.; Takahashi, K.;
Ishihara, J.; Hatakeyama, S. Tetrahedron 2006, 62, 38. (d) Nakano, A.;
Takahashi, K.; Ishihara, J.; Hatakeyama, S. Org. Lett. 2006, 8, 5357. (e)
Iwabuchi, Y.; Furukawa, M.; Esumi, T.; Hatakeyama, S. J. Chem. Soc.,
Chem. Commun. 2001, 2030. (f) Iwabuchi, Y.; Sugihara, T.; Esumi, V.;
Hatakeyama, S. Tetrahedron Lett. 2001, 42, 7867.
(1) Reviews: (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem.
ReV. 2003, 103, 811. (b) Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511.
(c) Declerck, V.; Martinez, J.; Lamaty, F. Chem. ReV. 2009, 109, 1. (d)
Ciganek, E. Organic Reactions; Paquette, L., Ed.; Wiley: New York, 1997;
Vol. 51, p 201. (e) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron
1996, 52, 8001. (f) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
4653.
(2) (a) Masson, G.; Housseman, C.; Zhu, J. Angew. Chem., Int. Ed. 2007,
46, 4514. (b) Shi, Y. L.; Shi, M. Eur. J. Org. Chem. 2007, 18, 2905. (c)
Basavaiah, D.; Rao, K. V.; Reddy, R. J. Chem. Soc. ReV. 2007, 36, 1581.
(5) (a) Shi, M.; Xu, Y.-M. Angew. Chem., Int. Ed. 2002, 41, 4507. (b)
Shi, M.; Xu, Y.-M.; Shi, Y.-L. Chem.sEur. J. 2005, 11, 1794.
10.1021/ol901920s CCC: $40.75
Published on Web 09/23/2009
 2009 American Chemical Society

able,8 making the access to both enantiomers of aza-MBH
adducts difficult.9 Intriguingly, it was noticed that the sense
of asymmetric induction in the ꢀ-ICD-catalyzed aza-MBH
reactions depended on the structure of electron-poor alkenes.
Indeed, the aza-MBH reaction of methyl or ethyl vinyl ketone
(MVK or EVK) with N-tosylimine afforded the (R)-enriched
allylamine, whereas the (S)-enriched allylamine was obtained
when acrylates, acrylonitrile, and acrolein were used as
Michael acceptors.5,6
We also surmised that in the presence of this dual catalyst
the enantioselectivity of the aza-MBH reflected directly that
of the Mannich reaction. On the basis of this mechanistic
assumption, we assumed that this dual catalytic system (1
and 2) should favor the (S)-aza-MBH product regardless of
the nature of Michael acceptor used and set out to investigate
the reaction between N-tosylimine 3 and MVK 4 which is
known to provide the (R)-aza-MBH adduct. We report herein
that the presence of an achiral additive (2) can indeed switch
the enantioselectivity from R to S for the aza-MBH reaction
between 3 and 4. We also identified a new ꢀ-ICD-amide 1e,
which in combination with 2 was highly efficient for the
access of (S)-5 from 3 and 4.
We recently reported that 6′-deoxy-6′-acylamino-ꢀ-ICD
(ꢀ-ICD-amide, 1b, Table 1) was capable of catalyzing the
We initially selected (E)-N-benzylidene-4-methoxybenzene
sulfonamide (3a) and MVK 4a as model substrates. Perform-
ing the reaction in the presence of ꢀ-ICD-amides (1b, R )
BocNHCH2, 0.1 equiv, CH2Cl2) and ꢀ-naphthol (2a, 0.1
equiv), the (S)-adduct 5a was indeed isolated in 99% yield
with 60% ee. Encouraged by this result, we screened ꢀ-ICD
and various ꢀ-ICD-amides10 with ꢀ-naphthol as cocatalyst.
The results are summarized in Table 1. In general, the ꢀ-ICD-
amides gave higher yields of the aza-MBH product than
ꢀ-ICD. The catalysts having an aromatic residue at the C-6′
position (1d-1f) were found to be more efficient than those
bearing an aliphatic chain (1b, 1c), with 1e (R1 ) 9-anthra-
cenyl) being the most effective (ee: 89%, entry 9). It has to
be noted that, in the absence of 2a, all these ꢀ-ICD-based
catalysts afforded the (R)-5a, albeit with reduced ee, indicat-
ing thus the crucial role of the achiral additive in achieving
the S-selectivity.11,12 We have also briefly examined the
effect of other achiral protic additives. As is seen, addition
of 3,5-bis(trifluoromethyl)phenol (2b) and 4-methoxyphenol
(2c) instead of naphthol (2a) into the catalytic reaction
afforded (S)-5a in excellent yields but with diminished ee
(entries 7, 8, vs 5). Both (R)- and (S)-BINOL were used in
association with 1e, and the (S)-adduct was obtained with
reduced enantioselectivity regardless of the absolute config-
uration of the BINOL (entries 10 and 11). These experiments
Table 1. Dual Enantioselective aza-MBH Reaction: Survey of
Catalysisa
entry cat. temp
additive
yieldb (%) eec (%)
1d
2
3
1a
1a
1b
1c
1d
1d
1d
1d
1e
1e
1e
1e
1e
1f
-30 none
26
39
99
>99
>99
80
-44 (R)
55 (S)
60 (S)
72 (S)
73 (S)
-69 (R)
46 (S)
59 (S)
89 (S)
51 (S)
60 (S)
84 (S)
-39 (R)
71 (S)
-52 (R)
96 (S)
-50 ꢀ-naphthol 2a
-30 ꢀ-naphthol 2a
-30 ꢀ-naphthol 2a
-30 ꢀ-naphthol 2a
-30 none
-30 3,5-CF3-C6H3OH 2b
-30 4-MeO-C6H4OH 2c
-30 ꢀ-naphthol 2a
-30 (R)-BINOL 2d
-30 (S)-BINOL 2e
-30 ꢀ-naphthol 2a
-30 none
4
5
6d
7
95
8
9
>99
>99
>99
>99
83
71
>99
91
10
11
12e
13d
14
15d
16
-30 ꢀ-naphthol 2a
-30 none
-50 ꢀ-naphthol 2a
1f
1e
>99
(9) Other enantioselective catalysts, see: (a) Matsui, K.; Takizawa, S.;
Sasai, H. J. Am. Chem. Soc. 2005, 127, 3680. (b) Matsui, K.; Tanaka, K.;
Horii, A.; Takizawa, S.; Sasai, H. Tetrahedron: Asymmetry 2006, 17, 578.
(c) Takizawa, S.; Matsui, K.; Sasai, H. J. Synth. Org. Chem. Jpn. 2007, 65,
1089. (d) Matsui, K.; Takizawa, S.; Sasai, H. Synlett 2006, 761. (e) Shi,
M.; Chen, L. H. Chem. Commun. 2003, 1310. (f) Shi, M.; Chen, L.-H.; Li,
C.-Q. J. Am. Chem. Soc. 2005, 127, 3790. (g) Shi, M.; Chen, L. H.; Teng,
W.-D. AdV. Synth. Catal. 2005, 347, 1781. (h) Liu, Y.-H.; Chen, L. H.;
Shi, M. AdV. Synth. Catal. 2006, 348, 973. (i) Shi, M.; Chen, L. H.; Li,
C.-Q. Tetrahedron: Asymmetry 2005, 16, 1385. (j) Qi, M.-J.; Ai, T.; Shi,
M.; Li, G. Tetrahedron 2008, 64, 1181. (k) Raheem, I. T.; Jacobsen, E. N.
AdV. Synth. Catal. 2005, 347, 1701. (l) Gausepohl, R.; Buskens, P.; Kleinen,
J.; Bruckmann, A.; Lehmann, C. W.; Klankermayer, J.; Leitner, W. Angew.
Chem., Int. Ed. 2006, 45, 3689. (m) Garnier, J.-M.; Anstiss, C.; Liu, F.
AdV. Synth. Catal. 2009, 351, 331. (n) Garnier, J.-M.; Liu, F. Org. Biomol.
Chem. 2009, 7, 1272.
a Reaction conditions: imine (3a) (0.1 mmol), MVK (4a) (0.2 mmol),
additive 2 (0.01 mmol), 1 (0.01 mmol) in CH2Cl2 (0.35 mL) for 48 h.
b Isolated yield after column chromatography. c Determined by chiral HPLC
analysis. d Reaction time: 72 h. e With 5 mol % of 2a.
enantioselective aza-MBH reaction between N-sulfonylimines
and ꢀ-naphthyl acrylate and documented that the presence
of an achiral additive ꢀ-naphthol (2a) can significantly
improve the ee of the product 5.10 A nucleophilic addition
of the Z-enolate onto the Re-face of the E-imine was
proposed to account for the observed S-enantioselectivity.
(10) Abermil, N.; Masson, G.; Zhu, J. J. Am. Chem. Soc. 2008, 130,
12596.
(6) Kawahara, S.; Nakano, A.; Esumi, T.; Iwabuchi, Y.; Hatakeyama,
S. Org. Lett. 2003, 5, 3103.
(11) Shi and co-workers have recently reported a substrate-directed
reversal of enantioselectivity by using salicyl N-tosylimines. (a) Shi, M.;
Qi, M.-J.; Liu, X.-G. Chem. Commun. 2008, 6025. The effect of the ortho-
hydroxy group on enantiodivergent phosphoric acid-catalyzed Povarov
reaction has also been reported. See: (b) Akiyama, T.; Morita, H.; Fuchibe,
K. J. Am. Chem. Soc. 2006, 128, 13070. (c) Liu, H.; Dagousset, G.; Masson,
(7) Balan, D.; Adolfsson, H. Tetrahedron Lett. 2003, 44, 2521.
(8) (a) Nakano, A.; Ushiyama, M.; Iwabuchi, Y.; Hatakeyama, S. AdV.
Synth. Catal. 2005, 347, 1790. (b) Nakano, A.; Takahashi, K.; Ishihara, J.;
Hatakeyama, S. Heterocycles 2005, 66, 371. Raheem, I. T.; Goodman, S. N.;
Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 706. (c) Igarashi, J.;
Katsukawa, M.; Wang, Y.-G.; Acharya, H. P.; Kobayashi, Y. Tetrahedron
Lett. 2004, 45, 3783.
G.; Retailleau, P.; Zhu, J. J. Am. Chem. Soc. 2009, 131, 4598
(12) 1a-catalyzed reaction between 3a and MVK leading to (R)-adduct
in 85% yield and 97% ee in DMF-MeCN. See ref 5.
.
Org. Lett., Vol. 11, No. 20, 2009
4649

indicated that the sense of asymmetric induction came from
mainly the bifunctional catalyst 1e rather than the chirality
of protic additive. Overall, naphthol (2a) was identified as
the best cocatalyst for this reaction. When the loading of 2a
was lowered to 5 mol %, both the yield and enantioselectivity
decreased slightly (Table 1, entry 12). By performing the
reaction at -50 °C in the presence of 1e and 2a (10 mol %
each), we were pleased to find that (S)-5a can be produced
in quantitative yield with 96% ee (entry 16).
> 97%). As expected, the (R)-enriched adduct was again
obtained in the absence of 2a (entry 9).
The use of aliphatic imines in an enantioselective aza-MBH
reaction is a long-standing problem due to their rapid degrada-
tion under experimental conditions.5,9,13 Delightfully, reaction
of aliphatic imines with MVK or EVK under our optimized
conditions furnished, in the presence of 4 Å molecular sieves,
the corresponding aza-MBH adducts 5m-r in good to
excellent enantioselectivities, albeit with moderate yields.
The invertible enantioselectivity in 1e-catalyzed aza-MBH
reaction between N-sulfonylimine 3 and MVK (4) is
demonstrated in Scheme 1. Thus, reaction of sulfonylimine
Having established that naphthol (2a) can inverse the
enantioselectivty of 1e-catalyzed aza-MBH reaction between
3a and 4a, we next examined the scope of the reaction using
MVK and EVK as Michael acceptors and a range of
sulfonylimines 3 as electrophiles. As shown in Table 2, the
Scheme 1
.
Dual Enantioselectivity of 1e-Catalyzed MBH
Reaction and Role of Naphthol 2a
Table 2. Enantioselective aza-MBH Reaction with
Representative Aromatic and Aliphatic N-Sulfonylimines
entry
R1
R2
product yieldb (%) eec (%)
1a
2a
3a
4a
5a
6a
7a
8a
9a
p-MeC6H4 (3b) Me (4a)
p-MeOC6H4 (3c) Me (4a)
p-CF3C6H4 (3d) Me (4a)
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
>99
62
96
96
95
94
96
97
98
96
>99
>99
>99
>99
>99
85
p-ClC6H4 (3e)
m-BrC6H4 (3f)
Me (4a)
Me (4a)
3b with MVK (4a) in DMF/CH3CN5 in the presence of
catalyst 1e afforded the (R)-5b in 58% yield with 89% ee.
The same reaction performed in CH2Cl2 in the presence of
1e and cocatalyst 2a provided (S)-5b in 99% yield with 96%
ee (Scheme 1).
The ability of ꢀ-naphthol 2a to inverse the enantioselec-
tivity of ꢀ-ICD-amide-catalyzed reaction between sulfo-
nylimines and MVK/EVK is intriguing.14 The R-selectivity
m-MeC6H4 (3g) Me (4a)
o-BrC6H4 (3h) Me (4a)
PhCHdCH (3i) Me (4a)
C6H5 (3a)
Et (4b)
Et (4b)
Et (4b)
Me (4a)
>99(46)d 98(-68)d
10a p-MeC6H4 (3b)
11a p-ClC6H4 (3e)
12e i-PrCH2 (3j)
>99
>99
59
71
42
46
36
37
98
97
81
85
90
92
93
93
13e c-hexylCH2 (3k) Me (4a)
14e n-butyl (3 L)
15e n-pentyl (3m)
16e Ph(CH2)2 (3n)
17e n-pentyl (3o)
Me (4a)
Me (4a)
Me (4a)
Et (4b)
(13) For elegant alternatives, see: (a) Zhang, Y.; Liu, Y.-K.; Kang, T.-
R.; Hu, Z.-K.; Chen, Y. C. J. Am. Chem. Soc. 2008, 130, 2456. (b)
Kamimura, A.; Okawa, H.; Morisaki, Y.; Ishikawa, S.; Uno, H. J. Org.
Chem. 2007, 72, 3569. (c) Utsumi, N.; Zhang, H.; Tanaka, F.; Barbas, C. F.,
III. Angew. Chem., Int. Ed. 2007, 46, 1878. (d) Cassani, C.; Bernardi, L.;
Fini, F.; Ricci, A. Angew. Chem., Int. Ed. 2009, 48, 5694. For ethylgly-
oxylate-derived imine, see: (e) Shi, M.; Ma, G.-N.; Gao, J. J. Org. Chem.
a Reaction conditions: imine (3) (0.1 mmol), 4 (0.2 mmol), ꢀ-naphthol
(2a) (0.01 mmol), 1e (0.01 mmol) in CH2Cl2 (0.35 mL) at -50 °C for
48 h. b Isolated yield after column chromatography. c Determined by chiral
HPLC analysis. d In the absence of ꢀ-naphthol (2a) with 1d as catalyst in
CH2Cl2 (c ) 0.35) at -30 °C. e Reaction conditions: aliphatic imine (3a)
(0.1 mmol), 4 (0.2 mmol), ꢀ-naphthol (2a) (0.01 mmol), 1e (0.01 mmol)
in CH2Cl2 (0.35 mL) at 0 °C for 12 h.
2007, 72, 9779
.
(14) Achiral additives reverse the enantioselectivity. For reviews, see:
(a) Sibi, M. P.; Liu, M. Curr. Org. Chem. 2001, 5, 719. (b) Zanoni, G.;
Castronovo, F.; Franzini, M.; Vidari, G.; Giannini, E. Chem. Soc. ReV. 2003,
32, 115. (c) Tanaka, T.; Hayashi, M. Synthesis 2008, 3361. For selected
examples, see: (d) Kobayashi, S.; Ishitani, H. J. Am. Chem. Soc. 1994, 116,
4083. (e) Gothelf, K. V.; Hazell, R. G.; Jørgensen, K. A. J. Org. Chem.
1998, 63, 5483. (f) Kawamura, M. Tetrahedron Lett. 1999, 40, 3213. (g)
Evans, D. A.; Kozlowski, M. C.; Murray, J. A.; Burgey, C. S.; Campos,
K. R.; Connell, B. T.; Staples, R. J. J. Am. Chem. Soc. 1999, 121, 669. (h)
Yabu, K.; Masumoto, S.; Yamasaki, S.; Hamashima, V.; Kanai, M.; Du,
W.; Curran, D. P.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 9908. (i)
Sibi, M. P.; Gorikunti, U.; Liu, M. Tetrahedron 2002, 58, 8357. (j) Bertozzi,
F.; Pineschi, M.; Macchia, F.; Arnold, L. A.; Minnaard, A. J.; Feringa,
B. L. Org. Lett. 2002, 4, 2703. (k) Zhou, J.; Ye, M. C.; Huang, Z. Z.;
Tang, Y. J. Org. Chem. 2004, 69, 1309. (l) Trost, B. M.; Fettes, A.;
Shireman, B. T. J. Am. Chem. Soc. 2004, 126, 2660. (m) Arseniyadis, S.;
Valleix, A.; Wagner, A.; Mioskowski, C. Angew. Chem., Int. Ed. 2004, 43,
3314. (n) Du, M.; Lu, S. F.; Fang, T.; Xu, J. J. Org. Chem. 2005, 70, 3712.
(o) Lutz, F.; Igarashi, T.; Kawasaki, T.; Soai, K. J. Am. Chem. Soc. 2005,
127, 12206. (p) Berkessel, A.; Mukherjee, S.; Lex, J. Synlett 2006, 41. (q)
Kitagawa, O.; Matsuo, S.; Yotsumoto, K.; Taguchi, T. J. Org. Chem. 2006,
71, 2524. (r) Zeng, W.; Chen, G.-Y.; Zhou, Y.-G.; Li, Y.-X. J. Am. Chem.
Soc. 2007, 129, 750.
catalysis showed substantial generality resulting in broad
substrate scope. Imines derived from aromatic aldehydes
bearing electron-donating and electron-withdrawing substit-
uents at the para, meta, and ortho positions were all tolerated
to afford cleanly the corresponding (S)-adducts in excellent
yields and enantioselectivities (entries 1-11). The R,ꢀ-
unsaturated imine 3i was also a suitable substrate providing
(S)-5i in 85% yield and 96% ee. Under the identical reaction
conditions (0.1 equiv of 1e, 0.1 equiv of 2a, CH2Cl2, -50
°C), the reaction of ethyl vinyl ketone (EVK, 4b) with
sulfonylimines proceeded smoothly to afford the (S)-aza-
MBH adducts in excellent yields and enantioselectivities (ee
4650
Org. Lett., Vol. 11, No. 20, 2009

in the ꢀ-ICD-catalyzed reaction between N-sulfonylimines
and MVK was explained by evoking a nonselective Mannich
reaction and a faster ꢀ-elimination of the (2S,3R)- vs (2S,3S)-
Mannich adduct (Scheme 2).5-7,9k,15 This implied that the
hypothesized that the Mannich reaction may become highly
stereoselective in the presence of ꢀ-naphthol (2a) to afford
the (2S,3S) adduct 9 via a ternary Z-enolate complex 8.
Subsequent ꢀ-naphthol-assisted ꢀ-elimination via a plausible
six-membered cyclic transition state 9 would then provide
the observed (S)-aza-MBH adduct. When the O-triflate ꢀ-ICD
(1g) lacking amide NH functionality was used in combination
with naphthol (2), the reaction between 3a and 4a gave the
aza-MBH (S)-5a adduct in 98% yield with much reduced
ee (48%). This control experiment indicated that both the
amide-NH in 1e and phenol-OH in 2 were important for
the high enantioselectivity observed in the present catalytic
system.
Scheme 2. Dual Enantioselectivity: Role of Achiral Additive
In summary, we reported that an achiral protic additive
was capable of inversing the ꢀ-ICD and ꢀ-ICD-amide-
catalyzed enantioselective aza-MBH reaction between N-
sulfonylimines and MVK/EVK, therefore providing a solu-
tion to the enantio-complementarity associated with this
family of catalysts.18-20 Further studies to elucidate the role
of ꢀ-naphthol are under active pursuit in our laboratory.
Acknowledgment. Financial support from CNRS and
ICSN is gratefully acknowledged. N.A. thanks ICSN for a
doctoral fellowship.
Supporting Information Available: Experimental pro-
cedures, product characterization, ee measurement, absolute
configuration determination for 5a and 5o, and copies of the
1H and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL901920S
(17) MBH and aza-MBH accelerated in the presence of protic solvents.
See: (a) Ameer, F.; Drewes, S. E.; Freese, S.; Kaye, P. T. Synth. Commun.
1988, 18, 495. (b) Bailey, M.; Marko´, I. E.; Ollis, D.; Rasmussen, P. R.
Tetrahedron Lett. 1990, 31, 4509. (c) Auge´, J.; Lubin, N.; Lubineau, A.
Tetrahedron Lett. 1994, 35, 7947. (d) Rezgui, F.; Gaied, M. M. E.
Tetrahedron Lett. 1998, 39, 5965. (e) Yu, C.; Liu, B.; Hu, L. J. Org. Chem.
2001, 66, 5413. (f) Cai, J.; Zhou, Z.; Zhao, G.; Tang, C. Org. Lett. 2002,
4, 4723. (g) Yamada, Y. M. A.; Ikegami, S. Tetrahedron Lett. 2000, 41,
2165. (h) Aggarwal, V. K.; Emme, I.; Fulford, S. Y. J. Org. Chem. 2003,
68, 692, and references cited therein.
proton migration step determined the enantioselectivity of
the reaction and that the reaction itself could be regarded as
a dynamic kinetic resolution. The ability of ꢀ-naphthol to
inverse the kinetics of these two competitive ꢀ-elimination
processes was not obvious. The recent mechanistic investiga-
tions carried out by Leitner16 and Aggarwal15b,c showed that
the addition of a Brønsted acid in aza-MBH reaction leads
to a shift of the rate-determining step (RDS) from the proton
migration to the Mannich-type coupling.17 We therefore
(18) Matched/mismatched enantioselective MBH and aza-MBH reaction,
see: (a) Shi, M.; Jiang, J.-K. Tetrahedron: Asymmetry 2002, 13, 1941. (b)
Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett. 2003, 5, 3741
.
(19) Effect of achiral additive on the yield and ee of aza-MBH reaction
has been reported. See for examples: (a) Shi, Y.-L.; Shi, M. AdV. Synth.
Catal. 2007, 349, 2129. See also: (b) Aroyan, C. E.; Vasbinder, M. M.;
(15) (a) Price, K. E.; Broadwater, S. J.; Jung, H. M.; McQuade, D. T.
Org. Lett. 2005, 7, 147. (b) Robiette, R.; Aggarwal, V. K.; Harvey, J. N.
J. Am. Chem. Soc. 2007, 129, 15513. (c) Aggarwal, V. K.; Fulford, S. Y.;
Miller, S. J. Org. Lett. 2005, 7, 3849
(20) Asymmetric organic catalysis with modified cinchona alkaloids,
see: Tian, S. K.; Chen, Y. G.; Hang, J. F.; Tang, L.; McDaid, P.; Deng, L.
.
Lloyd-Jones, G. C. Angew. Chem., Int. Ed. 2005, 44, 1706
(16) Buskens, P.; Klankermayer, J.; Leitner, W. J. Am. Chem. Soc. 2005,
127, 16762.
.
Acc. Chem. Res. 2004, 37, 621
.
Org. Lett., Vol. 11, No. 20, 2009
4651